In one aspect, this invention relates to a chemical purification process. In another aspect, the invention relates to a container for chemicals. In another aspect, the invention relates to a clean-up kit for use with radioisotopes prior to the manufacture of radiopharmaceutical products with such radioisotopes.
Lutetium-177 is a radioisotope which is used for radio-diagnostic and radio-therapeutic purposes. Lutetium-177 (atomic number 71) has a half-life of about 6.71 days and decays by emission of an electron to form hafnium-177 (atomic number 72). The short half-life is beneficial from the standpoint of quickly breaking down when administered to a patient, but is problematic from the standpoint of requiring extremely prompt (and careful) handling of the material between the producer of the radioisotope and the patient. Delays between the time of production of the material and its incorporation into a pharmaceutical material, and its administration to a patient result in a decrease in the amount of Lutetium-177, with a resultant decrease in radioactive potency (curies/volume), and a concomitant increase in the concentration of the hafnium decay product (mass/volume).
Lutetium-177 is typically received for the preparation of a radiopharmaceutical in a small glass vial which contains a specific dose of Lutetium-177 chloride in hydrochloric (HCl) acid solution. The dose is typically measured by the radioactive output of the vial, typically in millicuries. The radioactive output is typically a calculated value for a specific time and day. In order to deliver the calculated dose to a target site, it is necessary to transfer all of the Lutetium-177 in the vial to the target site at the indicated time.
Delivery is typically accomplished by incorporating the Lutetium-177 into a radiopharmaceutical product. This is typically done by reacting the Lutetium-177 with an organic moiety, such as a peptide or chelator, which will seek the target site when introduced into the patient. The stoichiometries of the reactions between the Lutetium-177 and the organic moiety, and the radiopharmaceutical and the target site, however, is complicated by the presence of the hafnium, and may be further complicated by the presence of further impurities commonly found in Lutetium-177 solution, such as iron, lead, zinc, aluminum, copper and calcium.
The hafnium competes with the Lutetium-177 for reaction with the organic moiety, and the hafnium-pharmaceutical competes with the Lutetium-177 radiopharmaceutical for binding with the target site. The efficacy with which a given radioactive dose of Lu-177 can be converted into a target-seeking form and delivered to the target site is thus highly dependent on the Lu/Hf ratios at each stage of the process. Stoichiometry is also complicated by the fact that a significant portion of the Lutetium-177 cannot be easily removed from the vial. Apparently, a portion of the lutetium can become chemically bound to the glass. Further, the amount of hafnium which is present can be greater than the amount calculated as being present from the decay of the Lutetium-177. Apparently, hafnium, as well as other impurities which are inherent to the glass, can be leached out by the solution from the inside of the glass vial.
The glass wall of the vial causes a further complication in delivering a prescribed radioactive dose to the target site. The actual output of the radioactive material in the vial is often different from the measured radioactive output from the vial, due to attenuation or radioactive shielding by the glass wall of the vial, and can be as much as 50% higher.
Simple techniques for removing the hafnium from the Lutetium-177 solution and for getting all of the Lutetium-177 from the vial would be very desirable, as this would enable higher quantities of ultra-pure Lutetium-177 to be delivered to the target site.
Techniques for providing ultra-pure Lutetium-177 to the end user, and for enabling the end user to better assess the potency of the dose of Lutetium-177 to be administered would also be desirable.